title: miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1.
abstract: Tumor angiogenesis is a critical process during cancer progression that modulates tumor growth and metastasis. Here, we identified an anti-angiogenic microRNA, miR-320, which is decreased in oral squamous cell carcinoma (OSCC) cell lines and tumor tissues from OSCC patients, down-regulated in blood vessels and inversely correlated with vascularity in OSCC tissues. Neuropilin 1 (NRP1), an important regulator of angiogenesis, was found to be a target of miR-320. The 3'-untranslated region of NRP1 mRNA contains multiple miR-320 binding sites, and its expression was regulated by miR-320. By administering either miR-320 precursor or antagonist, we found that miR-320 suppressed the migration, adhesion and tube formation of vascular endothelial cells. Knockdown of NRP1 abolished antagomiR-320-induced cell migration. Additionally, miR-320 expression was regulated by hypoxia in growth factor-deficient conditions by the hypoxia-inducible factor 1-alpha. Furthermore, lentivirus carrying the miR-320 precursor suppressed the tumorigenicity of OSCC cells and tumor angiogenesis in vivo. Taken together, these data show that miR-320 regulates the function of vascular endothelial cells by targeting NRP1 and has the potential to be developed as an anti-angiogenic or anti-cancer drug.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Wu
authors.forename: Yuh-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Yun-Chia
authors.initials: YC
authors.lastname: Jao
authors.forename: I-Shan
authors.initials: IS
authors.lastname: Hsieh
authors.forename: Kung-Chao
authors.initials: KC
authors.lastname: Chang
authors.forename: Tse-Ming
authors.initials: TM
authors.lastname: Hong
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039942:Neuropilin-1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D039942:Neuropilin-1